The current state of free radicals in Parkinson's disease. Nigral iron as a trigger of oxidative stress.
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Free Radicals↗
Biomedical subjects
A Friedman
Publications and source records attributed to A Friedman.
Health behavior in a kibbutz population: correlations among different modalities of healthcare utilization.
BACKGROUND: Alternative medicine use is increasing worldwide and the associated expenditures are significant. In Israel 19% of patients who consulted their family physician had also sought treatment by an alternative medicine practitioner. OBJECTIVES: To explore the correlation between different modalities of healthcare utilization, health behavior, and health belief among adult members of a kibbutz (rural communal settlement). This unique study population enabled the use of a simplified quantitative model due to the minimal individual differences in cost and access. METHODS: Healthcare utilization data were obtained for 220 kibbutz members aged 15-70 years from patient medical files and self-administered questionnaires over a 45 month period. Patient visits to the family practitioner and other specialist physicians were tallied, and individuals reported alternative medicine consultations during the previous year. Multiple regression analysis was used to control for age, chronic disease, and other background characteristics. RESULTS: The mean number of patient FP visits was 3.6 per patient per year. Women and chronic disease sufferers visited the doctor more frequently. A patient's number of FP visits and other specialist physician visits were closely correlated, with each specialist physician consult resulting in an additional 0.64 FP visit for a given individual (P = 0.007). Our analysis indicated that self-reported alternative therapy utilization was positively associated with the number of FP visits; patients reporting alternative therapy use visited their primary care physician once additionally per year (P = 0.03). Low self-rated health status was correlated with increased likelihood of alternative therapy use (borderline significance). CONCLUSION: These results suggest that a patient who seeks treatment from one type of healthcare practitioner will seek out other practitioners as well. This study supports the notion that unconventional therapies are used in conjunction with, rather than instead of, mainstream medical care.
Adolescent↗
Botulinum toxin for treatment of parkinsonian sialorrhea.
AIM: Sialorrhea is one of the main problems of patients with Parkinson's disease (PD). Most of the medications used for the treatment of it are ineffective. We decided to try in such patients local injections of botulinum toxin, type A, into both parotid glands. MATERIAL: 11 patients with clinical diagnosis of idiopathic PD and drooling assessed as at least 2 point on the UPDRS part II and 14 control subjects. METHODS: Salivation was measured by weighting dental rolls before and 2 minutes after insertion at 6 places of highest secretion of saliva in mouth (buccal vestibule, and sublingual area). PD patients were assessed before and one week after injections of 5 units of BOTOX into each parotid salivary gland and the results were compared to the salivation of controls. RESULTS: Average excretion of saliva in PD patients was significantly higher than in controls -0.39 +/- 0.4 g/2 min. (range: 0.02-1.82) vs. 0.19 +/- 0.16 g/2 min. (range: 0.02-0.98) (p = 0.03). After the treatment the average excretion of saliva in PD patients decreased to 0.25 +/- 0.26 g/2 min. (range: 0.004-0.99) and did not differ significantly from controls. All patients improved also according to UPDRS. No side-effects were observed in any of the patients injected. CONCLUSION: Botulinum toxin may be an effective and safe treatment of parkinsonian sialorrhea.
Aged↗
Posttransplant bone disease: evidence for a high bone resorption state.
Loss of bone is a significant problem after renal transplant. Although bone loss in the first post transplant year has been well documented, conflicting data exist concerning bone loss after this time. It is equally unclear whether bone loss in long-term renal transplant recipients correlates with bone turnover as it does in postmenapausal osteoporosis. To examine these issues, we conducted a cross-sectional study to define the prevalence of osteoporosis in long-term (> 1 year) renal transplant recipients with preserved renal function (mean creatinine clearance 73 +/- 23 ml/min). Bone mineral density (BMD) was measured at the hip, spine and wrist by DEXA in 69 patients. Markers for bone formation (serum osteocalcin) and bone resorption [urinary levels of pyridinoline (PYD) and deoxypyridinoline (DPD)] were also measured as well as parameters of calcium metabolism. Correlations were made between these parameters and BMD at the various sites. The mean age of the patients was 45 +/- 11 years. Eighty eight percent of patients were on cyclosporine (12% on tacrolimus) and all but 2 were on prednisone [mean dose 9 +/- 2 mg/day)]. Osteoporosis (BMD more than 2.5 SD below peak adult BMD) at the spine or hip was diagnosed in 44% of patients and osteopenia was present in an additional 44%. Elevated levels of intact parathyroid hormone (i PTH) were observed in 81% of patients. Elevated urinary levels of PYD or DPD were present in 73% of patients and 38% had elevated serum levels of osteocalcin. Levels of calcium, and of 25(OH) and 1,25(OH)2 vitamin D were normal. In a stepwise multiple regression model that included osteocalcin, PYD, DPD, intact PTH, age, years posttransplant, duration of dialysis, cumulative prednisone dose, smoking, and diabetes: urinary PYD was the strongest predictor of bone mass. These results demonstrate that osteoporosis is common in long-term renal transplant recipients. The data also suggest that elevated rates of bone resorption contribute importantly to this process.
Adult↗
Immune responses of chickens to dietary protein antigens. I. Induction of systemic and intestinal immune responses following oral administration of soluble proteins in the absence of adjuvant.
Oral administration of protein antigens in solution leads to the development of oral tolerance in most mammals but rarely so in the chicken. As dietary proteins are not expected to be immunogenic, the present study was undertaken to evaluate immunological consequences following oral exposure to protein antigens in chicks, and to determine whether or not this form of antigen is ignored. Chicks and turkey poults were fed solutions containing bovine serum albumin (BSA), porcine serum albumin, beta-lactoglobulin or bovine hemoglobin over a period of 6 days (25mg/chick/day). At different time points after feeding serum and bile were examined for presence of specific antibodies by ELISA. Surprisingly, the fed antigens induced robust antibody responses in the absence of added adjuvant. This immune response was further characterised to show that (1) a daily feeding regimen was more immunogenic than single dose feedings, (2) by using a daily feeding regimen, as little as 2mg/chick/day was fully immunogenic, (3) effective immunization was attained in chicks older than 10 day of age, (4) the main antibody class in the serum was IgG, and (5) high IgA levels were detected in the bile after booster feedings. These observations are difficult to reconcile with current concepts on peripheral tolerance to innocuous antigens, and indicate that the bird regulates tolerance and response in a manner different from that described in mammals.
Adjuvants, Immunologic↗
Bone marrow-derived dendritic cells pulsed with tumor homogenate induce immunity against syngeneic intracerebral glioma.
To evaluate the efficacy and toxicity of dendritic cell (DC) based therapy for intracerebral gliomas, we utilized a cell line derived from an astrocytoma that arose spontaneously in a VM/Dk mouse. This astrocytoma mirrors human gliomas phenotypically, morphologically and secretes transforming growth factor (TGF)-betas, immunosuppressive cytokines secreted by human gliomas. Systemic vaccination of mice with DCs pulsed with tumor homogenate followed by intracranial tumor challenge produced a > 160% increase in median survival (p = 0.016) compared with mice vaccinated with PBS or unpulsed DCs (p = 0.083). Fifty percent of mice treated with pulsed DCs survived long-term. Immunologic memory was demonstrated by survival of mice rechallenged with tumor. Both cell-mediated and humoral immunity was induced. On histological examination only focal areas of demyelination at the tumor implantation site were present. There was no evidence that autoimmune encephalomyelitis was induced by DC vaccination. Therefore, in a murine model, vaccination with DCs pulsed with glioma tumor homogenate is a safe and effective therapy against a syngeneic glioma located in the immunologically privileged central nervous system (CNS).
Animals↗
Analysis of a mathematical model of the effect of inhibitors on the growth of tumors.
In this paper, we study a model of tumor growth in the presence of inhibitors. The tumor is assumed to be spherically symmetric and its boundary is an unknown function r=R(t). Within the tumor the concentration of nutrient and the concentration of inhibitor (drug) satisfy a system of reaction-diffusion equations. The important parameters are Lambda(0) (which depends on the tumor's parameters when no inhibitors are present), gamma which depends only on the specific properties of the inhibitor, and beta; which is the (normalized) external concentration of the inhibitor. In this paper, we give precise conditions under which there exist one dormant tumor, two dormant tumors, or none. We then prove that in the first case, the dormant tumor is globally asymptotically stable, and in the second case, if the radii of the dormant tumors are denoted by R(s)(-),R(s)(+) with R(s)(-) infinity)R(t)=R(s)(-), provided the initial radius R(0) is smaller than R(s)(+); if however R(0)R(s)(+) then the initial tumor in general grows unboundedly in time. The above analysis suggests an effective strategy for treatment of tumors.
Antineoplastic Agents↗
Using renal transplantation to evaluate a simple approach for predicting the impact of end-stage renal disease therapies on patient survival: observed/expected life span.
The effectiveness of therapy for a chronic disease can be assessed by evaluating the length of time that a patient survives after receiving treatment. We used a novel means for measuring the effectiveness of renal replacement therapy for patients with end-stage renal disease (ESRD): the ratio of observed life span divided by expected life span. This ratio incorporated observed life span for patients from the time of ESRD and expected life span based on state-specific life-table analyses. A total of 3,782 individuals with ESRD were analyzed (average follow-up, 14.2 +/- 4.9 years); 3, 192 patients in that group received a kidney transplant at some point during their course of ESRD. For each patient, we determined a curve of observed/expected life span. Separate patient groups were analyzed to determine the median population observed/expected life span or the percentage of patients who reached 0.5 observed/expected life span. Younger transplant recipients (<21 years) had a median observed/expected life span of 67%, significantly greater than the median observed/expected life span for those aged 21 to 40 years (49%; P = 0.01) and 41 to 60 years (47%; P = 0.01). Surprisingly, 57% of the patients aged older than 60 years reached their median observed/expected life span (P = 0.02 versus <21 years; P = not significant against all others). A Cox proportional hazards model identified era of immunosuppression (hazards ratio, 0.32) and atherosclerotic vascular disease-related ESRD (hazards ratio, 2.07) as significant variables influencing patient survival and observed/expected life span. This simple ratio is easy to use and may be a helpful tool for assessing the survival benefits of risk-factor modifications and therapeutic advances in transplantation and ESRD care.
Adult↗
The team concept in mandibular reconstruction after ablative oncologic surgery.
PURPOSE: This study evaluated the efficiency and cost-effectiveness of using a reconstructive team for mandibular reconstruction. METHODS: An outcome-based retrospective review of 64 patients who had undergone microvascular fibular reconstruction of the mandible was performed. Operating room time, use of blood products, intraoperative fluid replacement, and hospital and intensive care unit stay were evaluated. Patients were divided into 2 groups on a chronologic basis. Group 1 was the first 34 consecutive patients and group 2 was the next 30 consecutive patients. RESULTS: Group 2 had a significantly shorter operating room time (P < .0001), hospital stay (P = .012), and used significantly less blood (P = .002) and colloid (P = .044) than group 1, resulting in significant cost savings, ($5,061.47/patient). Analysis showed no differences between groups demographically or for wound complications. CONCLUSIONS: Experience and the development of a team concept significantly decreased the cost for mandibular reconstruction with free fibula flaps without increasing wound complications.
Anesthesiology↗
Reasoning about geography.
To understand the nature and etiology of biases in geographical judgments, the authors asked people to estimate latitudes (Experiments 1 and 2) and longitudes (Experiments 3 and 4) of cities throughout the Old and New Worlds. They also examined how people's biased geographical judgments change after they receive accurate information ("seeds") about actual locations. Location profiles constructed from the pre- and postseeding location estimates conveyed detailed information about the representations underlying geography knowledge, including the subjective positioning and subregionalization of regions within continents; differential seeding effects revealed between-region dependencies. The findings implicate an important role for conceptual knowledge and plausible-reasoning processes in tasks that use subjective geographical information.
Adult↗
Updating geographical knowledge: principles of coherence and inertia.
In 2 experiments, the authors investigated how representations of global geography are updated when people learn new location information about individual cities. Participants estimated the latitude of cities in North America (Experiment 1) and in the Old and New Worlds (Experiment 2). After making their first estimates, participants were given information about the latitudes of 2 cities and asked to make a second set of estimates. Both the first and second estimates revealed evidence for psychologically distinct geographical subregions that were coordinated, in an ordinal sense, across the Atlantic Ocean. Further, the second estimates were affected by the nature of the physical adjacency between regions (e.g., the southern U.S. and Mexico) and by accurate location information about distant, but coordinated, subregions (e.g., the southern U.S. and Mediterranean Europe). The data provide support for a framework for making geographical estimates in which people strike a balance between 2 principles: the need to keep their knowledge base coherent, and the inertial tendency to resist changing the knowledge base unless it is necessary to maintain coherence.
Cognition↗
Role of tumor necrosis factor alpha and its type I receptor in luteal regression: induction of programmed cell death in bovine corpus luteum-derived endothelial cells.
The role of tumor necrosis factor alpha (TNF alpha) and its type I receptor (TNFRI) in structural luteolysis was investigated. A semiquatitative reverse-transcription polymerase chain reaction (RT-PCR) was used to characterize the pattern of TNFRI mRNA expression within the corpus luteum (CL) throughout the estrous cycle and its cellular distribution. Increase in TNFRI mRNA levels was recorded both in regressed luteal tissue and in CL of cows injected with prostaglandin F(2 alpha). All three major cell types composing the CL, steroidogenic (large and small) and endothelial cells expressed the TNFRI gene. A densitometric analysis of TNFRI mRNA expression revealed that resident endothelial cells had significantly higher levels of TNFRI mRNA than steroidogenic luteal cells. The physiological effects associated with TNFRI expression were investigated in the various luteal cell types. TNF alpha-induced programmed cell death (PCD) in dose- and time-dependent manners of cultured luteal endothelial cells (LECs) but not of in vitro luteinized steroidogenic cells. Several lines of evidence are provided to show that progesterone regulates luteal cell survival: 1) CL and LECs express progesterone receptor mRNA, 2) physiological levels of the steroid abolished TNF alpha-induced PCD of LECs, and 3) progesterone-producing cells are protected from PCD. In conclusion, this study suggests that TNF alpha-induced PCD during structural luteolysis is mediated by TNFRI, primarily affects endothelial cells, and that the decline in progesterone, preceding structural luteolysis, is a prerequisite for the initiation of apoptosis in endothelial cells.
Animals↗
Spinal nerve function in five volunteers experiencing transient neurologic symptoms after lidocaine subarachnoid anesthesia.
UNLABELLED: The etiology of transient neurologic symptoms (TNS) after 5% lidocaine spinal anesthesia remains undetermined. Previous case reports have shown that patients acutely experiencing TNS have no abnormalities on neurologic examination or magnetic resonance imaging. The aim of our study was to determine whether volunteers with TNS would exhibit abnormalities in spinal nerve electrophysiology. Twelve volunteers with no history of back pain or neurologic disease underwent baseline electromyography (EMG), nerve conduction studies, and somatosensory-evoked potential (SSEP) testing. Then, the volunteers were administered 50 mg of 5% hyperbaric lidocaine spinal anesthesia and were placed in a low lithotomy position (legs on four pillows). The next day, all volunteers underwent follow-up EMG, nerve conduction, and SSEP testing and were questioned and examined for the presence of complications including TNS (defined as pain or dysthesia in one or both buttocks or legs occurring within 24 h of spinal anesthesia). Volunteers who had TNS underwent additional EMG testing 4-6 wk later. Five of the 12 volunteers reported TNS. No volunteer had an abnormal EMG, nerve conduction study, or SSEP at 24 h follow up, nor were there any changes in EMG studies at delayed testing in the five volunteers experiencing TNS. On statistical analysis, the right peroneal and the right tibial nerve differed significantly for all volunteers from pre- to postspinal testing. When comparing pre- and postspinal testing of the TNS and non-TNS volunteers, statistically significant changes occurred in the nerve conduction tests of the right peroneal and left tibial nerve. There was no difference in measurements of F response, H reflex latency, amplitude, or velocity for either leg. Multivariate analysis of variance showed no significant difference between TNS and non-TNS volunteers for the changes in the nine nerve conduction tests when considered together (P = 0.4). We conclude that acute TNS after lidocaine spinal anesthesia did not result in consistent abnormalities detectable by EMG, nerve conduction studies, or SSEP in five volunteers. IMPLICATIONS: Electrophysiologic testing in volunteers experiencing transient neurologic symptoms is not abnormal.
Adult↗
Images in cardiology. Giant right coronary artery fistula in a neonate.
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Coronary Vessel Anomalies↗
Psychological functioning in children and adolescents with Sturge-Weber syndrome.
Previous studies of individuals with Sturge-Weber syndrome have focused on the medical aspects of this syndrome, but little has been known about the affective and behavioral correlates. We collected psychological and medical data from parents and teachers for 79 children and adolescents with Sturge-Weber syndrome and a group of their siblings. We also obtained the results of intellectual assessment for a subset of the Sturge-Weber syndrome group. The young people with Sturge-Weber syndrome exhibited more problems than the group of siblings across a number of behavioral domains: intellectual/academic, social skills, mood, and compliance. Those children most at risk for psychological problems were those with lower levels of intellectual functioning, those with seizure disorders, and those with more frequent seizures. Larger port-wine stains were also associated with an increase in mood and social problems but only for older children. Increased age was not associated with lower levels of intellectual or academic functioning, but mood and social problems were more common in older children.
Achievement↗
Resident curriculum guidelines for neurosurgery. Congress of Neurological Surgeons Education Committee.
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Curriculum↗
Enhancement of DNA vaccine potency using conventional aluminum adjuvants.
The immunogenicity and protective efficacy of DNA vaccines have been amply demonstrated in numerous animal models of infectious disease. However, the feasibility of DNA vaccines for human use is not yet known. In order to investigate potential means of increasing the potency of DNA vaccines, conventional adjuvants such as aluminum salts were tested. Coadministration of these adjuvants with DNA vaccines substantially enhanced the ability of these vaccines to induce antibody responses up to 100-fold in mice and guinea pigs, and 5-10-fold in non-human primates. Effective formulations had no demonstrable effect on the levels of antigen expression in situ and consisted of adjuvants that did not form complexes with the plasmid DNA; rather they exerted their effects on antigen after expression in situ. Therefore, the potency of DNA vaccines both in laboratory rodents and in non-human primates can be substantially increased by simple formulation with conventional aluminum adjuvants.
Adjuvants, Immunologic↗
Anticholinesterases induce multigenic transcriptional feedback response suppressing cholinergic neurotransmission.
Cholinesterase inhibitors (anti-ChEs) include a wide range of therapeutic, agricultural and warfare agents all aimed to inhibit the catalytic activity of the acetylcholine (ACh) hydrolysing enzyme acetylcholinesterase (AChE). In addition to promoting immediate excitation of cholinergic neurotransmission through transient elevation of synaptic ACh levels, anti-ChEs exposure is associated with long-term effects reminiscent of post-traumatic stress disorder. This suggested that exposure to anti-ChEs leads to persistent changes in brain proteins and called for exploring the mechanism(s) through which such changes could occur. For this purpose, we established an in vitro system of perfused, sagittal mouse brain slices which sustains authentic transcriptional responses for over 10 h and enables the study of gene regulation under controlled exposure to anti-ChEs. Slices were exposed to either organophosphate or cabamate anti-ChEs, both of which induced within 10 min excessive overexpression of the mRNA encoding the immediate early response transcription factor c-Fos. Twenty minutes later we noted 8-fold increases over control levels in AChE mRNA, accompanied by a 3-fold decrease in the mRNAs encoding for the ACh synthesizing enzyme choline acetyltransferase (ChAT) and the vesicular ACh transporter (VAChT). No changes were detected in synaptophysin mRNA levels. These modulations in gene expression paralleled those taking place under in vivo exposure. Of particular concern is the possibility that feedback processes leading to elevated levels of brain AChE may be similarly associated with low-level exposure to common organophosphorous anti-cholinesterases, and lead to long-term deleterious changes in cognitive functions.
Acetylcholinesterase↗